Pacylex Pharmaceuticals announced today the dosing of the first patient in a new Phase 1/2 clinical trial evaluating zelenirstat in patients with relapsed or refractory acute myeloid leukemia (AML). This milestone marks a significant advancement in the company's development of novel N-myristoyltransferase inhibitors (NMTis) for cancer treatment.
Zelenirstat, formerly known as PCLX-001 or DDD86481, represents a pioneering approach as the first-in-class NMTi to enter clinical development. The oral, small-molecule drug has shown promising results in preclinical studies and earlier clinical investigations.
Mechanism of Action and Preclinical Evidence
The drug works by inhibiting N-myristoyltransferase, an enzyme responsible for myristoylation—a process critical for the function of numerous proteins involved in cancer cell survival and proliferation. In laboratory studies, zelenirstat has demonstrated selective cytotoxicity against AML cell lines and patient samples.
"Zelenirstat triggers apoptosis and cell death through multiple mechanisms, including in AML stem cells, which are often responsible for disease relapse," explained Michael J. Weickert, Ph.D., CEO of Pacylex Pharmaceuticals. "This unique mechanism of action provides a novel approach to treating this challenging disease."
Preclinical data showed that the compound can regress hematologic malignancies and inhibit the growth of lung and breast cancer tumors in animal models, suggesting potential broader applications.
Clinical Development Path
The current trial (ClinicalTrials.gov ID NCT06613217) follows the successful completion of a Phase 1 multiple ascending dose study in patients with relapsed/refractory lymphoma and refractory solid tumors. That initial study demonstrated an acceptable safety and tolerability profile, pharmacokinetics supporting once-daily oral dosing, and early signs of efficacy.
"The progression to AML represents a strategic expansion of zelenirstat's development program," noted Weickert. "Based on our Phase 1 results, which showed good safety and significant progression-free and overall survival benefits in solid tumor patients, we're optimistic about the potential impact for AML patients who currently have limited treatment options."
Regulatory Support and Funding
The U.S. Food and Drug Administration (FDA) has granted zelenirstat both Orphan Drug Designation and Fast Track Designation for AML, highlighting the significant unmet medical need in this patient population. AML is the most common acute leukemia in adults, with approximately 20,000 new cases diagnosed annually in the United States. Despite advances in treatment, the five-year survival rate remains below 30%, with significantly worse outcomes for relapsed or refractory patients.
The clinical investigation is supported by a grant from the U.S. Department of Defense, with previous funding for the company's research coming from the Cure Cancer Foundation, Alberta Cancer Foundation, and Alberta Innovates.
Broader Pipeline Development
Beyond zelenirstat, Pacylex is developing a portfolio of 27 additional potent NMTis as potential payloads for antibody-drug conjugates (ADCs) targeting solid tumors. This approach could potentially expand the therapeutic applications of NMT inhibition to a wider range of cancers.
"We're positioning Pacylex as the world leader in developing N-myristoyltransferase inhibitors for cancer treatment," said Weickert. "Our dual focus on hematologic malignancies with oral zelenirstat and solid tumors with our ADC payload candidates represents a comprehensive approach to addressing significant unmet needs in oncology."
Headquartered in Edmonton, Alberta, with an additional office in the San Francisco Bay area, Pacylex continues to advance its clinical programs while exploring partnership opportunities to accelerate development.
The company has not disclosed a timeline for when initial results from the AML trial might be available, but the Fast Track designation could potentially expedite the development process if early data prove promising.
